血浆NCAM/ABCA1双标外泌体内Aβ42和microRNA-388-5p在阿尔茨海默病早期诊断中的价值

凌四海; 支杨; 李莹; 陈霞利; 刘辰庚

doi:10.3784/jbjc.202201190005

血浆NCAM/ABCA1双标外泌体内Aβ42和microRNA-388-5p在阿尔茨海默病早期诊断中的价值

doi: 10.3784/jbjc.202201190005

凌四海^1,,
支杨²,
李莹³,
陈霞利¹,
刘辰庚^1, ,

1.
首都医科大学附属北京安定医院检验科, 北京 100053
2.
北京市西城区广外医院检验科, 北京 100055
3.
中国人民解放军空军医学特色中心检验科, 北京 100142

基金项目: 北京市属医院科研培育计划（No. PX2022077）；国家自然科学基金（No. 81401734）；国家重点研发计划（No. 2019YFF0216502）

详细信息

作者简介:
凌四海，女，湖南省长沙市人，硕士，副主任技师，主要从事疾病监测和诊断标志物筛选工作，Email: lingsihai@mail.ccmu.edu.cn

通讯作者:
刘辰庚， Tel：010–58303217，Email：brown117@163.com

中图分类号: R211; R446.1
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- 文章访问数: 41
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- 被引次数: 0
出版历程
- 收稿日期: 2022-01-19
- 网络出版日期: 2022-05-27
- 刊出日期: 2022-07-14

Value of plasma NCAM/ABCA1 double-labeled exosomal Aβ42 and microRNA-388-5p in early diagnosis of Alzheimer's disease

1.
Clinical Laboratory of Xuanwu Hospital, Captital Medcial University, Beijing 100053, China
2.
Xicheng District Guangwai Hospital, Beijing 100055, China
3.
Clinical Laboratory, Air Force Medical Center, Beijing 100142, China

Funds: This study was supported by the fund for Beijing Municipal Administration of Hospitals Incubating Program (No. PX2022077), the National Natural Science Foundation of China (No. 81401734) and the fund for National Key Research and Development Program of China (No. 2019YFF0216502)

摘要

摘要: 目的检测神经细胞黏附分子（NCAM）和三磷酸腺苷（ATP）结合盒转运体A1（ABCA1）双标记外泌体内Aβ42和microRNA-388-5p（miR-388-5p），并分析其在阿尔茨海默病（AD）早期诊断中的潜在价值。方法检测67例主观认知下降（SCD）、65例遗忘型轻度认知障碍（aMCI）、68例痴呆期阿尔茨海默病（DAT）患者、60例健康对照组受试者及60例血管性痴呆（VaD）的疾病对照组患者的血浆NCAM/ABCA1外泌体Aβ42和miR-388-5p水平，分析各指标间的相关性及其对疾病发展阶段的诊断效能。结果 SCD、aMCI和DAT受试者血浆NCAM/ABCA1双标外泌体Aβ42水平均显著高于VaD和健康对照组受试者（P<0.05）；SCD、aMCI和DAT受试者血浆NCAM/ABCA1双标外泌体miR-388-5p含量均显著低于VaD及对照组受试者（P<0.05）。血浆NCAM/ABCA1双标外泌体内Aβ42对SCD、aMCI和DAT诊断的敏感度和特异度均高于miR-388-5p。结论本研究提示NCAM/ABCA1双标外泌体中Aβ42和miR-388-5p可作为aMCI和SCD诊断或预警的候选标志物，但尚需纵向多中心研究以进一步证实。
- 阿尔茨海默病 /
- 诊断 /
- 外泌体 /
- β-淀粉样蛋白 /
- 微小核糖核酸
Abstract: Objective To detect the dual-labeled Aβ42 and miR-388-5p in exosomes of nerve cell adhesion molecule (NCAM) and ATP binding cassette transporter A1 (ABCA1), and analyze their potential value in the early diagnosis of Alzheimer's disease (AD). Methods The levels of plasma NCAM/ABCA1 exosomes Aβ42 and miR-388-5p of 67 cases of subjective cognitive decline (SCD), 65 cases of amnestic mild cognitive impairment (aMCI), 68 Alzheimer's disease cases with dementia (DAT), 60 healthy controls and 60 controls of vascular dementia (VaD) cases were detected, and the correlation between the indicators and the diagnostic power of each disease stage were analyzed. Results The plasma levels of NCAM/ABCA1 double-labeled exosomes Aβ42 in SCD, aMCI and DAT cases were significantly higher than those in controls of VaD cases and healthy controls (P<0.05). In plasma NCAM/ABCA1 of SCD, aMCI and DAT cases, the content of miR-388-5p in double-labeled exosomes was significantly lower than those of controls of VaD cases and healthy controls (P<0.05). The sensitivity and specificity of plasma NCAM/ABCA1 double-labeled exosomal Aβ42 for SCD, aMCI and DAT were higher than those of miR-388-5p. Conclusion This study suggests that Aβ42 and miR-388-5p in NCAM/ABCA1 double-labeled exosomes can be used as candidate markers for the diagnosis or early warning of aMCI and SCD, but longitudinal multicenter studies are still needed to further confirm the results.
- Alzheimer's disease /
- Diagnosis /
- Exosome /
- Amyloid β /
- MicroRNA

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图 1 受试者工作特征曲线

注： SCD、aMCI和DAT患者血浆总Aβ42（A）和miR-388-5p（B）相对健康对照组的ROC曲线； SCD、aMCI和DAT患者外周血NCAM/ABCA1双标外泌体内Aβ42（C）和miR-388-5p（D）相对健康对照组的ROC曲线。SCD. 主观认知下降；aMCI. 遗忘型轻度认知障碍；DAT. 痴呆期阿尔茨海默病；ROC.受试者工作特征

Figure 1. ROC curve

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表 1 不同受试组总Aβ42和双标外泌体内Aβ42的吸光度

Table 1. Total Aβ42 and Aβ42 absorbance in double-labeled exosomes in different groups

分组	总Aβ42	双标外泌体内Aβ42	P值
分组	总Aβ42	双标外泌体内Aβ42	与DAT比较	与aMCI比较	与SCD比较	与VaD比较
对照组	3.12±0.59	1.03±0.28	0.003/<0.001	0.028/<0.001	0.092/0.019	0.139/0.088
VaD	3.09±0.61	1.08±0.31	0.007/<0.001	0.039/<0.001	0.188/0.065	1.000/1.000
SCD	2.93±0.56	1.36±0.33	0.013/<0.001	0.072/0.008	1.000/1.000	0.188/0.065
aMCI	2.81±0.43	2.01±0.35	0.009/<0.001	1.000/1.000	0.072/0.008	0.039/<0.001
DAT	2.56±0.38	3.09±0.43	1.000/1.000	0.009/<0.001	0.013/<0.001	0.007/<0.001
注：P值分别表示为总Aβ42/双标外泌体内Aβ42与不同受试组的两两比较。VaD. 血管性痴呆；SCD. 主观认知下降；aMCI. 遗忘型轻度认知障碍；DAT. 痴呆期阿尔茨海默病；P值栏数据表示为“总Aβ42组间比较的P值/双标外泌体内Aβ42组间比较的P值”

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表 2 不同受试组总MiR-388-5p和双标外泌体内MiR-388-5p的水平

Table 2. Total MiR-388-5p and double-labeled exosome MiR-388-5p levels in different groups

分组	总miR-388-5p	双标外泌体内miR-388-5p	P值
分组	总miR-388-5p	双标外泌体内miR-388-5p	与DAT比较	与aMCI比较	与SCD比较	与VaD比较
对照组	1.51±0.35	2.93±0.49	0.002/<0.001	0.033/<0.001	0.102/0.025	0.156/0.093
VaD	1.55±0.43	0.82±0.43	0.013/<0.001	0.049/<0.001	0.233/0.036	1.000/1.000
SCD	1.35±0.29	2.38±0.35	0.025/<0.001	0.093/0.001	1.000/1.000	0.233/0.036
aMCI	1.22±0.23	1.33±0.20	0.002/<0.001	1.000/1.000	0.093/0.001	0.033/<0.001
DAT	0.77±0.11	0.81±0.13	1.000/1.000	0.002/<0.001	0.025/<0.001	0.013/<0.001
注：P值分别表示总miR-388-5p /双标外泌体内miR-388-5p与不同受试组的两两比较。VaD.血管性痴呆；SCD. 主观认知下降；aMCI. 遗忘型轻度认知障碍；DAT. 痴呆期阿尔茨海默病；P值栏数据表示为“总miR-388-5p组间比较的P值/双标外泌体内miR-388-5p组间比较的P值”

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表 3 各组内Aβ42与miR-388-5p相关性分析

Table 3. Correlation analysis between Aβ42 and miR-388-5p in each group

Aβ42与 miR-388-5p来源	对照组		VaD		SCD		aMCI		DAT		总体分析
Aβ42与 miR-388-5p来源	r值	P值	r值	P值	r值	P值	r值	P值	r值	P值	r值	P值
血浆总量	0.491	0.003	0.438	0.017	0.382	0.035	0.417	0.011	0.450	0.009	0.423	0.021
血浆双标外泌体	−0.634	<0.001	−0.672	<0.001	−0.528	<0.001	−0.692	<0.001	−0.685	<0.001	−0.653	<0.001
注：P值表示为相关性分析的统计结果。VaD. 血管性痴呆；SCD. 主观认知下降；aMCI. 遗忘型轻度认知障碍；DAT. 痴呆期阿尔茨海默病

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表 4 受试者工作特征曲线和诊断效能分析结果

Table 4. Receiver operating characteristic curve and diagnostic performance analysis results

分组	来源	项目	曲线下面积	标准误	95%置信区间		截断值	P值	敏感度（%）	χ²值	特异度（%）	χ²值
分组	来源	项目	曲线下面积	标准误	下限	上限	截断值	P值	敏感度（%）	χ²值	特异度（%）	χ²值
SCD	血浆总体	Aβ42	0.525	0.019	0.506	0.544	1.29	0.002	62.5	38.969	66.3	37.592
	血浆总体	miR-388-5p	0.529	0.029	0.500	0.558	2.93	0.001	61.5	38.969	63.3	37.592
	外泌体内	Aβ42	0.683	0.029	0.654	0.712	1.02	0.006	73.5^a	48.956	71.4^a	51.015
	外泌体内	miR-388-5p	0.615	0.020	0.595	0.635	2.77	<0.001	67.3	48.956	66.3	51.015
aMCI	血浆总体	Aβ42	0.677	0.021	0.656	0.698	1.98	0.005	68.6	36.957	68.3	37.569
	血浆总体	miR-388-5p	0.621	0.020	0.601	0.641	1.85	0.017	67.2	36.957	67.5	37.569
	外泌体内	Aβ42	0.739	0.031	0.701	0.770	1.77	0.003	72.3	39.871	71.9	36.755
	外泌体内	miR-388-5p	0.662	0.023	0.639	0.685	1.65	<0.001	69.5	39.871	70.3	36.755
DAT	血浆总体	Aβ42	0.771	0.030	0.741	0.801	3.01	0.003	70.2	38.215	70.1	37.567
	血浆总体	miR-388-5p	0.709	0.028	0.681	0.737	1.23	0.002	68.8	38.215	69.5	37.567
	外泌体内	Aβ42	0.815	0.035	0.780	0.850	2.69	<0.001	79.3^a	45.639	81.3^a	47.051
	外泌体内	miR-388-5p	0.769	0.028	0.701	0.757	0.97	<0.001	73.1	45.639	75.7	47.051
注：a. 与同组的miR-388-5p相比P<0.05。SCD. 主观认知下降；aMCI. 遗忘型轻度认知障碍；DAT. 痴呆期阿尔茨海默病

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